Isr J Psychiatry Relat Sci - Vol. 49 - No 2 (2012) Stress and Support for Parents of Youth with

Radha B. Nadkarni, PhD,1 and Mary A. Fristad, PhD2

1 Behavioral Health Services, Nationwide Children’s Hospital, Columbus, Ohio, U.S.A. 2 Departments of Psychiatry, Psychology & Human Nutrition, the Ohio State University, Columbus, Ohio, U.S.A.

Introduction ABSTRACT Raising a child with bipolar disorder (BD) is a daunting Background: This article reviews stress related to task. In addition to the struggles one can experience parenting a youth with bipolar disorder (BD), maladaptive simply obtaining an appropriate diagnosis, developing a coping, immunologic and physical functioning related to functional treatment plan, and dealing with the myriad ; presents preliminary findings about the of difficult symptoms at home and at school, stigma and association between immune parameters and health blame can further challenge parents, who often battle conditions, mental health indices and interpersonal mood disorders themselves, or in their immediate fam- functioning in parents of children with mood ily members (1). disorders; and provides recommendations for stress In this article, we review the literature on parenting management based on clinical trials of family-based psychoeducational psychotherapy (PEP). stress related to raising a child with BD. Next, we focus on stress associated with parental BD, as children with Data: Interleukin-6 (IL-6), tumor necrosis factor-alpha BD often have parents with a , adding (TNF-α), C-reactive protein (CRP), Epstein Barr Virus to the parenting challenge. Then, we discuss maladap- (EBV), nutritional markers and measures of physical tive coping related to chronic stress. Subsequently, we health, mental health and interpersonal functioning were provide findings from a pilot study that assessed immu- collected from 26 parents of mood disordered children. nologic functioning in caregivers of children with mood Higher CRP was associated with more perceived disorder. Finally, we suggest strategies to support par- stress, more , increased incidence of illness/ ents in managing the stress associated with parenting a physical conditions, and lower albumin levels. Elevated child with BD based on clinical trials of family-based IL-6 was associated with higher nicotine use. psychoeducational psychotherapy (PEP). Limitations: Sample size and demographics were restricted, limiting generalizability. Caregiver Stress Conclusion: Pilot data are consistent with literature Childhood onset BD is likely to be lifelong, with waxing from adult caregivers, and suggest caregivers who are and waning symptoms that require ongoing, active man- more stressed also evidence some signs of immune agement (2). As a result, caring for a child with BD can abnormality. Evidence-based strategies to support parents are discussed. be quite stressful and can adversely impact multiple areas of parents’ lives. Parents cope with a wide range of dif- ficulties that may include: diminished relationships with Financial support for this project obtained through a grant awarded friends and relatives; financial strain due to limited insur- to Dr. Mary A. Fristad from National Institute of Mental Health grant ance coverage for behavioral health care; and strains on # R01MH061512 and the Ohio Department of Mental Health (IRB# the caregiver’s emotional and physical health (3-5). 2004H0052). Dr. Fristad receives royalties from Guilford Press, Inc. for a treatment manual and from CFPSI for corresponding MF-PEP Even factors that might typically serve as protective and IF-PEP workbooks (www.moodychildtherapy.com). factors from stress, such as higher income and educa-

Address for Correspondence: Mary A. Fristad, PhD, ABPP, Department of Psychiatry, The Ohio State University, 1670 Upham Drive, Suite 460G, Columbus, OH 43210, U.S.A. [email protected]

104 Stress and Support for Parents of Youth with Bipolar Disorder tion levels, may not be sufficient to relieve the paren- Bidirectional causes of stress are common in families tal burden associated with caring for a child with BD. of children with BD. In addition to the stress of raising Hellander and colleagues (5) surveyed 732 caregivers of a child with BD, parents often have a mood disorder children with BD via the Child and Adolescent Bipolar themselves, further complicating family life. Foundation (CABF) website. Most respondents were female (97%), White (97%), married (75%), and finan- cially middle-class or above (two-thirds of respondents Parents with a Mood Disorder reported income over $50,000). Many were profes- Genetic risk. Mood disorders are highly heritable. sionals including doctors, teachers and social workers. Having a first degree relative with BD increases the risk Presumably, this sample had greater access to adequate of this illness 10-fold (7). Individuals with BD have an professional care for their children with BD than the increased likelihood of marrying a person with a mood overall population of parents raising children with BD. disorder, a phenomenon referred to as “assortative mat- Despite this, significant levels of stress were reported. ing” (7), which places the children of such couplings at an The three most stressful aspects of caregiving were: even higher risk for developing a mood disorder. A child “walking on the eggshells around child to avoid rages”; who has one parent with a mood disorder has a 27% life- “trying to get child to do chores or self-care”; and “hav- time risk of a mood disorder whereas a child who has ing less time to take care of self.” The authors speculated two parents with a mood disorder carries a 74% lifetime that caregivers from non-affluent and less educated risk (7). Thus, children with BD not infrequently have families would likely experience even more stress. This parents with a mood disorder. stress can be caused by many aspects of raising a child Psychosocial risk. In addition to the genetic risk, with BD, one common and particularly difficult phe- parental mood disorders may expose children to mal- nomenon being blame for the child’s symptoms. adaptive child rearing practices, which can contribute Historically parents of children with mood disorders to an earlier onset of disorder for the child and/or make have been blamed rather than supported in their par- recovery from an episode more prolonged (7-9) Even if enting (4). Caregivers report condemnation and social parents of children with BD do not have a mood disor- from family gatherings, church and community der themselves, they often have experienced the effects events, and extended social networks due to their child’s of BD within their family of origin. Having grown up difficult behavior and stigma associated with mental dis- with a parent or sibling who has BD colors what adults order (3, 5). Blame often includes the presumed etiology bring to their parenting. for their child’s mental illness and associated behavioral Several predictors of poorer outcome for adults with problems (6). Caregivers focus attention and devote time BD are also factors that increase familial stress. These to caregiving, leading to neglect of self and others in the include less social support and lower social adjustment family (5). Often parents develop and depressive (10), familial negative expressed and negative symptomatology associated with chronic stressors com- interaction (11), impaired social and leisure activi- parable to those described for caregivers of (6). ties, poor quality of relationship with extended family Attempting to obtain appropriate services or accom- (12), more stressful life events (13), and poorer marital modations can also be a challenging experience. Barriers adjustment (14). Targum and colleagues (15) found to receiving adequate care include: professionals not that the social problems that resulted from BD included believing parental report of behavior; professionals marital problems, unemployment, financial difficulties, insinuating that poor parenting strategies have caused social withdrawal due to depression, and relapse leading the child’s symptoms; and professionals who lack train- to re-hospitalization. ing and knowledge that results in inappropriate ques- Impact on parenting. Children benefit by consis- tioning, erroneous diagnosis, and unsuitable treatment tency in parenting behavior. When parents have BD, (1). In addition to not being helpful in the moment, consistency in parenting practices may be challenging. encounters such as this can prevent families from seek- Parenting behavior may be influenced by the parent’s ing professional assistance later in the course of the depression, mania/hypomania, or mixed state, chro- child’s development if they have learned through expe- nicity of episodes, suicidality/suicide attempts, risky rience that interventions costs them time, money and behavior associated with mania, difficulty with treat- without the benefit of symptomatic relief. ment adherence, withdrawn/irritable behavior during

105 Radha B. Nadkarni and Mary A. Fristad depressed mood, relapse in of treatment adher- including elevations in inflammatory markers (inter- ence, and recovery time between episodes. In sum, par- leukin-6 [IL-6], tumor necrosis factor - alpha [TNF- ents with a mood disorder experience life stressors due α], C-reactive protein [CRP] and Epstein Barr Virus to their own diagnosis. Raising a child with BD amidst [EBV]) (26-30). Elevations of proinflammatory cyto- these stressors can be challenging. kines (IL-6 and TNF -α), CRP and EBV have serious health consequences, including increased morbidity and mortality (28-30). Studies of the effects of poor Psychological and Physical health behaviors have found that alcohol abuse is asso- Consequences of Caregiving ciated with decreased natural killer cell activity and/ Clearly, parents of children with BD experience ongo- or daytime increase of IL-6 (31); cigarette smoking is ing stress. Prior research indicates that caregiving has associated with elevated levels of cortisol (32); caffeine long-term impact on psychological well-being even after is associated with increase in plasma ephinephrine and caregiving ceases. For example, in a study conducted cortisol (24); and depressive mood in individuals with by Robinson-Whelen and colleagues (16), even though obesity is associated with elevated levels of CRP (33). perceived stress and negative decreased in former Individuals who experience partial night sleep depriva- caregivers of a relative with a progressive dementing tion are prone to over-secrete IL-6 during the daytime illness, scores on measures of psychological well-being and under-secrete IL-6 during nighttime (34). This is a (depression, positive affect and ) did not return problem, as good quality night sleep is associated with to non-caregiver levels within three years after caregiv- decreased secretion of daytime IL-6 levels (35). Sleep ing demands ceased. The stress of caregiving for children deprivation elevates daytime IL-6 levels, resulting in with mental health problems, due to the physical and drowsiness and fatigue during the next day (35). Not emotional challenges involved in early years of caregiv- surprisingly, physical activity and exercise are associ- ing, lack of service coordination among service provid- ated with improved immune functioning, with regular ers, and inadequate time and energy for self care, might exercise producing anti-inflammatory effects (36). similarly negatively influence caregivers’ psychological well being and physical health in later years (17, 18). Numerous studies have linked chronic psychological Immune Functioning in Parents of stress and adverse health outcomes (19-22). For example, Children with Mood Disorder chronic has been associated with Immune dysregulation associated with caregiving stress increased risk for developing mild hypertension (19), has been studied in older adults (37, 38), but no studies hastening the progression of coronary artery disease (20), have assessed IL-6, TNF-α, CRP and EBV in parents of aggravating the course of rheumatoid arthritis (21), and children with mood disorders. To document the relation- increasing susceptibility to colds (22). Research further ship between stress and immune functioning in caregiv- indicates that individuals with chronic stress are more ers of children with mood disorder, IL-6, TNF-α, CRP, likely to abuse substances, including alcohol, nicotine EBV and health conditions, mental health indices and and caffeine, as a method of coping (23, 24). They are interpersonal functioning were measured in 26 caregiv- also likely to eat “comfort foods” instead of nutritionally ers of children participating in a family-based psychoso- healthy foods (25) and may have sleep-related prob- cial intervention for children with mood disorders. lems such as difficulty falling asleep, awakening in the middle of the night or waking in the early morning (26). Moreover, individuals with chronic stress may lack the Pilot Study time to devote to physical exercise and other healthy hab- Participants. Twenty-six caregivers (M = 41.0 years, its due to caregiving demands (27). This combination of SD = 6.2) from the Multi-Family Psychoeducational stress and maladaptive coping can also negatively influ- Psychotherapy (MF-PEP) treatment study participated ence physical health in later years (16). in this study after providing informed consent. Both this Chronic stress and poor health behaviors have also research study and the MF-PEP parent study, results of been linked to adverse immune and neuroendocrine which have been published elsewhere (39, 40), were consequences. Studies have shown that chronic stress approved by the university medical center Institutional and depression can provoke immune dysregulation, Review Board. Participants were primarily female

106 Stress and Support for Parents of Youth with Bipolar Disorder

(62%), White/Non-Hispanic (96%), had more than a Table 1. Pearson Product Moment Correlations between IL-6, high school education (92%), a family income between TNF-α, CRP, EBV and Physical Health Behaviors and Indices, $40,000-$80,000 (58%), and lived with a spouse who Mental Health Indices, and Measures of Interpersonal Functioning was the child’s other biological parent (58%). IL-6 TNF-α CRP EBV Measures. Levels of IL-6, TNF-α, CRP, EBV, and nutritional markers (total iron binding protein, plasma Variables r r R R transferrin and albumin) were assessed. Information Physical Health Behaviors and Indices regarding physical health (health-related behavior Alcohol -0.14 0.33 -0.1 -0.17 Caffeine 0.34* -0.32 -0.16 0.28 questions [26], physical activity (frequency of exercise Nicotine 0.67** -0.11 -0.06 -0.12 [41]; general health (questions from the Older Adults Physical activity 0.03 0.18 -0.15 -0.06 Resources Survey [42]); sleep (Pittsburgh Sleep Quality Weight changes -0.14 0.28 -0.03 -0.01 Index [43], parenting stress (Parent Stress Survey Sisson Medications -0.18 0.22 -0.11 -0.12 Illnesses 0.21 -0.27 0.58*** 0.004 [44]); depression (Center for Epidemiological Studies PSQI 0.13 0.16 0.1 -0.15 Depression Scale [45], anxiety (Beck Anxiety Inventory Nutritional Measures [46]), stress (Perceived Stress Scale [47]); interper- Albumin 0.21 -0.27 -0.54*** -0.23 sonal functioning (social functioning subscale, Older Transferrin 0.02 0.25 0.14 0.16 Americans Resources and Services Multidimensional TIB 0.01 0.25 0.14 0.16 Functional Assessment Questionnaire [42]); and parent- Mental Health Indices child relations (Expressed Emotion Adjective Checklist BAI -0.09 -0.24 -0.10 -0.70 [48]) were also collected. CES-D -0.21 0.23 0.50*** 0.05 a Data Analysis. Q-Q Plots were used to verify nor- PrSS -0.24 -0.009 0.37 0.08 PSS -0.21 0.17 0.58*** 0.22 mality of the distribution for IL-6, TNF-α, and CRP. Distributions for IL-6 and CRP were normal; however, Interpersonal Functioning the distribution for TNF-α was not. TNF-α values were EEAC 0.05 -0.09 -0.19 -0.02 OARS -0.22 0.27 -0.24 0.07 transformed by taking the reciprocal of the data, Q-Q plots were used to verify normality of the distribution of Note: IL-6 = Interleukin-6; TNF-α = tumor necrosis-alpha; CRP = C-reactive protein; EBV = Epstein Barr Virus; PSQI = Pittsburgh Sleep transformed data. To explore the relationship between Quality Index; TIB = Total Iron Binding; BAI = Beck Anxiety Inventory; immune parameters, nutritional markers, physical CES-D= Center for Epidemiological Studies Depression Scale; PrSS = Parent Stress Survey; PSS = Perceived Stress Scale; EEAC health conditions, health-related behaviors, mental = Expressed Emotion Adjective Checklist; OARS = Social support health indices, and interpersonal functioning, Pearson functioning from the Older Americans Resources and Services Product Moment correlations were calculated. As this Multidimensional Functional Assessment Questionnaire. an = 19 and for all remaining variables N = 26; * p = 0.09; ** p = 0.000; was an exploratory study, analyses were not corrected ***p ≤0.009 for the 68 multiple comparisons made; therefore, some significant findings could be expected by chance. who did not. Parents with higher CRP levels had lower Results and Discussion. Higher CRP levels were albumin levels. Higher serum albumin has a protective associated with lower levels of albumin, more illnesses/ effect in older individuals without cytokine-mediated physical conditions, higher perceived stress and higher inflammation (51). In short, preliminary results suggest reported depression levels (Table 1). Higher usage of that parents of children with mood disorders who are nicotine was associated with higher levels of IL-6. No more stressed are also showing some signs of immune significant relationships between TNF-α, EBV and abnormality. As these parents continue to age while car- other variables were detected. ing for their children, it will be important to provide Findings indicated that parents with higher CRP psychological interventions that target caregiving stress. levels had increased illnesses/physical conditions, Limitations. This pilot study was limited by the small consistent with past research indicating that eleva- and homogenous sample, thereby limiting the general- tions of proinflammatory cytokines have significant izability of results to other groups. health consequences (29, 30). Also consistent with past Conclusions. Parents of youth with BP may experi- research, higher CRP levels were associated with higher ence chronic stress due to the demands of caregiving perceived stress and depression (38, 49, 50). Parents and stigma associated with the disorder (52). Due to who used nicotine had higher levels of IL-6 than those the genetic aspect of BD, parents themselves may have

107 Radha B. Nadkarni and Mary A. Fristad a mood disorder, which can further exacerbate the situ- simply having a crisis plan defined and in place can ation. Instead of receiving support and understanding avert the frequency with which it actually needs to be from friends and/or family, community, social network, implemented. Pre-planning strategies might include: and church groups, parents may experience isolation, 1) preemptive visits to the local police precinct to and blame due to child’s difficult behavior. Chronic determine the most appropriate steps for calling the stress has been associated with decreased utilization of police, if needed to deescalate a violent situation; 2) healthy habits, immune dysregulation and poor physi- preparing and maintaining a binder that includes: the cal health outcomes. Long-term caregiving has clearly child’s list of medications and side effects, treatment documented consequences on emotional and physical providers’ names and emergency contact information; health, including immunologic functioning. Our pilot insurance information; 3) determining the route to the data suggest that parents of children with mood disorders most appropriate emergency department if hospital- who are more stressed also show some signs of immune ization is being considered; 4) developing “safe places” abnormality. Thus, interventions supportive of parents for siblings to go to during periods of escalation at may be particularly important, both for parents’ mental home. and physical well-being. Psychoeducational interventions are designed to provide social support, enhance cop- Improving Family Climate ing, encourage healthy behaviors (e.g., regarding sleep Learning to manage symptoms of BD in a matter of fact, hygiene, less nictone/smoking usage, diet and exercise) manner using clear, direct communica- and improve family climate; they may positively impact tion is highly beneficial in improving the emotional cli- these immune parameters in caregivers of children with mate in the home. Reducing critical, hostile, and over- mood disorders. Below we discuss components of family- involved family interactions, a trio of family interaction based psychoeducational psychotherapy, which can sup- behaviors referred to as “expressed emotion, or EE,” port parents as they care for children with BD. provides a more stable environment in which the child can recover. Asarnow and colleagues (55) have demon- strated that depressed children who return post-hos- Clinical Implications pitalization to a low EE environment are less likely to Utilizing Psychoeducational Psychotherapy (PEP) relapse over the course of a year than those who return Parents are ultimately responsible for the care of their to a high EE home. High EE is associated with increased child with BD; thus, it is imperative that mental health relapse rates in children and adults with BD (56, 57). providers make available interventions that provide the Moreover, higher maternal warmth is associated with information, support and skill building so that parents lower relapse rates post-recovery in youth with BD (58, can dismiss guilt and move forward productively with 59). This highlights the importance of treatments that their child to more effectively manage symptoms. This focus on family adaptability, cohesion and conflict (60). includes learning about various mood diagnoses, moni- Mediators of effective family interventions may include toring mood states, recognizing prodromal symptoms enhancing medication adherence, family communica- and patterns, developing strategies to enhance treat- tion, problem solving and ability to recognize prodro- ment adherence, understanding medication — how to mal symptoms (61). In addition to improved symptom monitor its effectiveness and manage side effects, safety management, overt attention to all relationships within planning for risky behaviors, building school and men- the family can improve family climate. This includes tal health treatment teams, and learning to differentiate making time for and valuing the marital/couple rela- the child from the disorder (2). This psychoeducational tionship and addressing sibling needs. approach has been demonstrated in three randomized controlled trials to improve outcomes for children and Maintaining Physical Health families (39, 53, 54), in part by helping parents become As evidenced by the immunologic data previously pre- better consumers of care (40). sented, the importance of maintaining physical health is important. This includes engaging in health behav- Pre-Planning For Crises iors such as regular check-ups, regular exercise, healthy Crisis pre-planning can decrease the emotional inten- eating habits and sufficient sleep. In addition to pro- sity that surrounds crisis points. In many families, moting “healthy habits” in children, parents can, and

108 Stress and Support for Parents of Youth with Bipolar Disorder should, role model reliance on these SEE (Sleep, Eating, Reducing Caregiving Burden Exercise) behaviors themselves. Accessing formal or informal respite care can allow for Improving quality of sleep can make a critical differ- parents to take a break as well as to meet other fam- ence for family functioning. Insufficient sleep can trig- ily obligations. While some formal respite is available ger a manic episode or intensify depressive symptoms. in many communities, most families do not have as Thus, sleep hygiene is important for all family members. much access to this formalized assistance as would be When a parent’s lack of sleep is secondary to - desired. Thus, helping parents to problem-solve how ing about a child’s risky behavior at night while manic, to arrange for additional informal respite can be a use- use of a motion detector on the door can provide some ful step in therapy. Informal respite might be available assurance of the child’s whereabouts. via extended family, supportive friends, church youth Eating habits are largely set by parents within a fam- groups, through a bartering arrangement (e.g., the ily. Thus, if children are to engage in eating nutritious parent might exchange gardening for a friend for that food that does not lead to excessive weight gain (a prob- friend taking the child with BD on a weekly outing), or lem for many children on weight-gaining medications), a paid provider such as a baby sitter. There are various parents typically need to be involved to plan, purchase ways of using respite time. Caregivers might use this and prepare the food. Including children in this process time to spend quality time with their significant other, is desirable, whenever possible. with the child’s siblings, to run errands alone, or to sim- Parents may choose to interact with their child ply do something relaxing alone or with friends. It is around exercise, such as going to the park together vital that parents not feel guilty about this “me” time. or playing together on a video/TV interactive game console, for example, or they may use exercise as their Increasing Social Support chance either for or adult interactions, perhaps Maintaining social networks via family, friends, neigh- going for a long run, or attending an exercise class or bors, religious communities and social networking game of basketball with friends. Regardless, engaging in all are options for parents. One specialized form of exercise both helps to promote health in the parent as social support comes from internationally accessible well as to model healthy behavior for the child. Internet support networks such as The Balanced Mind Foundation (formerly known as Child and Adolescent Maintaining Mental Health Bipolar Foundation, CABF). The Balanced Mind In addition to pursuing the previously described strate- Foundation has been found beneficial to parents for gies, attention to parental mental health is of obvious support and guidance as the website offers informa- critical importance. This can include seeking profes- tive resources, chat rooms, message boards and email sional assistance, be it psychotherapy and/or medica- support group (5). Other advocacy and support orga- tion management, as well as utilization of nizations include in the United States, Depression and techniques such as mindfulness meditation. A growing Bipolar Support Alliance (DBSA) and the National scientific literature supports the use of stress reduction Alliance on Mental Illness (NAMI) and in Israel, the via mindfulness practice. Studies have demonstrated Israel Mental Health Association (ENOSH). These that regular practice of various relaxation techniques organizations work with patients and their families can lower blood pressure, slow breathing rate, increase by offering educational programs, self-help support blood to major muscles, reduce muscle tension, groups, telephone hotlines for emergencies, referrals to reduce chronic , improve concentration, and reduce mental health professionals and newsletters. Moreover, and (62-64). No-cost relaxation tech- through advocacy parents may feel empowered as they niques such as self massage, guided imagery, yoga, pro- may be able to influence services and supports, and gressive muscle relaxation, Tai Chi and deep breathing fight stigma associated with the disorder, in turn giving can be useful for stress reduction. Again, utilization of them a sense of strength and control. Finally, face-to- these techniques can not only be beneficial to the par- face and Internet support groups provide a means to ent, but also provide good role modeling for the child, make new friends while learning tips from others with as some therapy manuals (e.g., MF-PEP) incorporate similar concerns. Information on these resources may breathing exercises for children and their parents as be made available to parents at their first appointment part of the overall intervention. through offices of mental health professionals.

109 Radha B. Nadkarni and Mary A. Fristad

longitudinal study of patients on prophylactic treatment. Acta Psychiatr Summary Scand 1996;93:420-426. Raising a youth with BD can be stressful. Our pilot data 13. Kulharaa P, Basua D, Mattooa SK, Sharana P, Choprab R. Lithium prophylaxis of recurrent bipolar affective disorder: Long-term outcome suggest that parents of children with mood disorders who and its psychosocial correlates. J Affect Disord 1999;54:87-96. are more stressed are also showing some signs of immune 14. Bauwens F, Tracy A, Pardoen D, Vander Elst M, Mendlewicz J. Social abnormality. Interventions may help caregivers avoid adjustment of remitted bipolar and unipolar out-patients. A comparison with age- and sex-matched controls. Br J Psychiatry 1991;159:239-244. premature aging of the immune system due to chronic 15. Targum SD, Dibble ED, Davenport YB, Gershon ES. The Family stress, which makes caregivers vulnerable to a range of Attitudes Questionnaire: Patients’ and spouses’ views of bipolar illness. diseases (37, 38, 50). Our previous RCTs of family-based Arch Gen Psychiatry 1981;38:562-568. 16. Robinson-Whelen S, Tada Y, MacCallum RC, McGuire L, Kiecolt- psychoeducational psychotherapy indicate that children Glaser JK. Long-term caregiving: What happens when it ends? J and parents benefit from psychoeducational interventions Abnorm Psychol 2001;110:573-584. designed to provide information, support and stress man- 17. Murphy N, Christian L, Caplin D, Young O. The health of caregivers for children with disabilities: Caregiver perspectives. Child Care Hlth Dev agement skill building. Reducing caregiving stress may 2007;33:180-187. positively impact immune parameters in caregivers of 18. Yatchmenoff DK, Koren PE, Friesen BJ, Gordon LJ, Kinney RF. children with mood disorder. Additional study of family- Enrichment and stress in families caring for a child with a serious based psychosocial interventions to aid the child and fam- emotional disorder. J Child Family Studies 1998;7:129-145. 19. Grant I, Adler KA, Patterson TL, Dimsdale JE, Ziegler MG, Irwin MR. ily in recovery from BD is recommended. Health consequences of Alzheimer’s caregiving transitions: Effects of placement and bereavement. Psychosom Med 2002;64:477-486. Acknowledgements 20. Vitaliano PP, Scanlan JM, Zhang J, Savage MV, Hirsch IB, Siegler IC. A We wish to acknowledge Ms. Katherine Mount, research assistant, for her path model of chronic stress, the metabolic syndrome, and coronary effort and time in compiling the references for this article. heart disease. Psychosom Med 2002;64:418-435. Author Contributions: Dr. Nadkarni was involved in analysis and interpretation 21. Zautra AJ, Burleson MH, Matt KS, Roth S, Burrows L. Interpersonal of data, drafting and final approval of this manuscript. Dr. Fristad was involved stress, depression, and disease activity in rheumatoid arthritis and in conception and design, collection, analysis and interpretation of data, osteoarthritis patients. Health Psychol 1994;13:139-148. critical revision and final approval of the manuscript. 22. Cohen S, Frank E, Doyle W, Skoner D, Rabin B, Gwaltney J. Types of stressors that increase susceptibility to the common cold in healthy adults. Health Psychol 1998;17:214-223. References 23. Goeders M. Stress, motivation, and drug addiction. Curr Dir Psychol 1. Mackinaw-Koons B, Fristad M. Children with bipolar disorder: How to Sci 2004;13:33-35. break down barriers and work effectively together. Prof Psychol Res Pr 24. Lane J, Adcock A, Williams R, Kuhn C. Caffeine effects on cardiovascular 2004;35:481-484. and neuroendorine responses to acute psychosocial stress and their 2. Fristad, MA, Goldberg-Arnold, JS, Leffler J. Psychotherapy for children relationship to level of habitual caffeine consumption. Psychosom Med with bipolar and depressive disorders. New York, N.Y.: Guilford, 2011. 1990;52:320-336. 3. Lefley H. Family burden and family stigma in major mental illness. Am 25. Dallman M, Pecoraro N, la Fleur S. Chronic stress and comfort Psychol 1989;44:556-560. foods: Self-medication and abdominal obesity. Brain Behav Immun 4. Hinshaw S. The stigmatization of mental illness in children and parents: 2005;19:275-280. Developmental Issues, family concerns, and research needs. J Child 26. Kiecolt-Glaser JK, Glaser R. Methodological issues in behavioral Psychol Psychiatry 2005;46:714-734. immunology research with humans. Brain Behav Immun 1988;2:67-78. 5. Hellander M, Sisson D, Fristad M. Internet support for parents of 27. Fristad M, Goldberg-Arnold JS. Family interventions for early-onset children with early-onset bipolar disorder. Bipolar disorder in childhood bipolar disorder. Bipolar disorder in childhood and early adolescence. and early adolescence. New York, N.Y.: Guilford, 2003: pp. 314-329. New York: Guilford, 2003: pp. 295-313. 6. Goldberg-Arnold J, Fristad M, Gavazzi S. Family psychoeducation: 28. Ridker, PM, Cushman, M, Stampfer M, Tracy R, Hennekens C. Giving caregivers what they want and need. Fam Relat 1999;48:411-417. Inflammation, aspirin, and the risk of cardiovascular disease in 7. Goodwin, FK, Jamison, KR. Bipolar disorder and recurrent depression. apparently healthy men. N Engl J Med 1997;336:973-979. Second edition. New York: Oxford University, 2007. 29. Harris R, Ferrucci L, Tracy R, Corti M, Wacholder S, Ettinger W, et al. 8. Kennard B, Hughes J, Stewart S, Mayes T, Nightengale-Teresi J, Tao Associations of elevated interleukin-6 and C-reactive protein levels with R. Maternal depressive symptoms in pediatric depressive disorder: mortality in the elderly. Am J Med 1999;106:506-512. Relationship to acute treatment outcome. J Am Acad Child Adolesc 30. Glaser R, Friedman S, Smyth J, Ader R, Bijur P, Cohen N. The differential Psychiatry 2008;47:694-699. impact of training stress and final examination stress on herpes virus 9. Weissman M, Warner V, Wickramaratne P, Moreau D, Olfson M. latency at the United States Military Academy at West Point. Brain Offspring of depressed parents: 10 years later. Arch Gen Psychiatry Behav Immun 1999;13:240-251. 1997;54:932-940. 31. Redwine L, Dang J, Hall M, Irwin M. Disordered sleep, nocturnal cytokines, 10. O’Connell R, Mayo J, Eng L, Jones J, Gabel R. Social support and long- and immunity in alcoholics. Psychosom Med 2003;65:75-85. term lithium outcome. Brit J Psychiatry 1985;147:272-275. 32. Steptoe A, Ussher M. Smoking, cortisol, and nicotine. Int J Psychophysiology 11. Miklowitz DJ. Psychosocial approaches to the course and treatment of 2006;59:228-235. bipolar disorder. CNS Spectrums 1998;3:48-52. 33. Ladwig K, Marten-Mittag B, Lowel H, Doring A, Koenig W. Influence of 12. Stefos G, Bauwens F, Staner L, Pardoen D, Mendlewicz J. Psychosocial depressive mood on the association of CRP and obesity in 3205 middle predictors of major affective recurrences in bipolar disorder: A 4-year ages healthy men. Brain Behav Immun 2003;17:268-275.

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34. Redwine L, Hauger RL, Gillin JC, Irwin M. Effects of sleep and sleep regulation of pro-inflammatory cytokines: A glucocorticoid-resistance deprivation on Interleukin-6, growth hormone, cortisol, and melatonin model. Health Psychol 2002;21:531-541. levels in humans. J Clin Endocr Meta 2000;85:3597-3603. 51. Reuben D, Ferrucci L, Wallace R, Tracy R, Chiara C, Heimovitz H, et 35. Vgontzas AN, Papanicolaou DA, Bixler EO, Lotsikas A, Zachman K, al. The prognostic value of serum albumin in healthy older persons Kales A, et al. Circadian Interleukin-6 secretion and quantity and depth with low and high serum interleukin-6 (IL-6) levels. J Am Geriatr Soc of sleep. J Clin Endocr Metab 1999;84(8):2603-2607. 2000;48:1404-1407. 36. Woods J. Physical activity, exercise, and immune function. Brain Behav 52. Mendenhall A, Mount K. Parents of children with mental illness: Immun 2005;19:369-370. Exploring the caregiver experience and caregiver-focused interventions. 37. Lutgendorf SK, Garand L, Buckwalter KC, Reimer TT, Hong S, Lubaroff Fam Soc 2011;92:183-190. DM. Life stress, mood disturbance, and elevated Interleukin-6 in 53. Fristad MA. Psychoeducational treatment for school-aged children with healthy older women. J Gerontol Series A: Biological Sciences and bipolar disorder. Dev Psychopathol 2006;18:1289-1306. Medical Sciences 1999;54:M434-M439. 54. Fristad MA, Goldberg-Arnold, JS, Gavazzi SM. Multi-family 38. Kiecolt-Glaser JK, Preacher KJ, MacCallum RC, Atkinson C, Malarkey psychoeducation groups in the treatment of children with mood WB, Glaser R. Chronic stress and age-related increases in the disorders. J Marital Fam Ther 2003;29:491-504. proinflammatory cytokine IL-6. Proc Natl Acad Sci USA 2003;100:9090- 55. Asarnow J, Goldstein M, Tompson M, Guthrie D. One-year outcomes 9095. of depressive disorder in child psychiatric in-patients: Evaluation of 39. Fristad M, Verducci J, Walters K, Young M. Impact of multifamily the prognostic power of a brief measure of expressed emotion. J Child psychoeducational psychotherapy in treating children aged 8 to 12 years Psychol Psychiatry 1993;34:129-137. with mood disorders. Arch Gen Psychiatry 2009;66:1013-1020. 56. Miklowitz DJ, Goldstein MJ, Nuechterlein KH, Snyder KS, et al. Family 40. Mendenhall A, Fristad M, Early T. Factors influencing service utilization factors and the course of bipolar affective disorder. Arch Gen Psychiatry and mood symptom severity in children with mood disorders: Effects of 1988;45:225-231. multifamily psychoeducation groups (MFPGs). J Consult Clin Psychol 2009;77:463-473. 57. Miklowitz DJ, Biuckians A, Richards JA. Early-onset bipolar disorder: A family treatment perspective. Dev Psychopathol 2006;18:1247. 41. Washburn R, Adams L, Haile G. Physical activity assessment for epidemiologic research: The utility of two simplified approaches. Prev 58. Geller B, Craney JL, Bolhofner K, Nickelsburg MJ, Williams M, Med 1987;16:626-646. Zimerman B. Two-year prospective follow-up of children with a prepubertal and early adolescent bipolar disorder phenotype. Am J 42. Fillenbaum GG, Smyer MA. The development, validity, and reliability Psychiatry 2002;159:927-933. of the Oars Multidimensional Functional Assessment Questionnaire. J Gerontol 1981;36:428-434. 59. Geller B, Tillman R, Craney JL, Bolhofner K. Four-year prospective outcome and natural history of mania in children with a prepubertal 43. Buysse D, Reynolds C, Monk T, Berman S, Kupfer D. Pittsburgh sleep and early adolescent bipolar disorder phenotype. Arch Gen Psychiatry quality index: A new instrument for psychiatric practice and research. 2004;61:459-467. Psychiatry Res 1989;28:193-213. 60. Miklowitz D, Axelson D, George E, Taylor D, Schneck C, Sullivan 44. Sisson D, Fristad M. A survey of stress and support for parents of A, et al. Expressed emotion moderate the effects of family-focused children with early-onset bipolar disorder. Bipolar Disord 2001;3:58. treatment for bipolar adolescents. J Am Acad Child Adolesc Psychiatry 45. Radloff LS. The CES-D Scale. Appl Psychol Meas 1977;1:385-401. 2009;48:643-651. 46. Beck AT, Epstein N, Brown G, Steer RA. An inventory for measuring 61. Miklowitz D. The role of family in the course and treatment of bipolar clinical anxiety: Psychometric properties. J Consult Clin Psychol disorder. Curr Dir Psychol Sci 2007;16:192-196. 1988;56:893-897. 62. Zeidan F, Johnson S, Gordon N, Goolkasian P. Effects of brief and sham 47. Cohen S, Kamarck T, Mermelstein R. A global measure of perceived mindfulness meditation on mood and cardiovascular variables. J Altern stress. J Health Soc Behav 1983;24:385-396. Complement Med 2010;16:867-873. 48. Friedmann, MS, Goldstein, MJ. Relatives’ awareness of their own 63. Streeter C, Whitfield T, Owen L, Rein T, Karri S, Yakhkind A, et al. expressed emotion as measured by a self-report adjective checklist. Fam Effects of yoga versus walking on mood, anxiety, and brain GABA Process 1993;32:459-471. levels: A randomized controlled MRS study. J Altern Complement Med 49. Pike J, Irwin M. Dissociation of inflammatory markers and natural 2010;16:1145-1152. killer cell activity in major depressive disorder. Brain Behav Immun 64. Kiecolt-Glaser J, Christian L, Preston H, Houts C, Malarkey W, Emery 2006;20:169-174. C, et al. Stress, inflammation, and yoga practice. Psychosom Med 50. Miller GE, Cohen S, Ritchey AK. Chronic psychological stress and the 2010;72:113-121.

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